Lhermitte-Duclos disease: A report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway

被引:63
作者
Abel, TW
Baker, SJ
Fraser, MM
Tihan, T
Nelson, JS
Yachnis, AT
Bouffard, JP
Mena, H
Burger, PC
Eberhart, CG
机构
[1] Johns Hopkins Univ, Dept Pathol, Div Neuropathol, Baltimore, MD USA
[2] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN USA
[3] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA
[4] Pacific Hlth Res Inst, Dept Pathol, Honolulu, HI USA
[5] Univ Hawaii, Honolulu, HI 96822 USA
[6] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA
[7] Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC USA
关键词
AKT; Cowden disease; dysplastic cerebellar gangliocytoma; Lhermitte-Duclos disease; mTOR; PTEN; S6;
D O I
10.1093/jnen/64.4.341
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in I I of them. We hypothesized that the granule cell hypertrophy in LDD is secondary to activation of mammalian target of rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major regulator of cell growth. Histopathologically, in addition to the classical findings of LDD, we observed prominent vascular proliferation and vacuolization of the white matter in many of the lesions. Four patients met diagnostic criteria for CD, and many of the remaining patients had some clinical features of CD. Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in the large ganglionic cells forming the lesions, indicating activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD. These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic, inhibition of mTOR.
引用
收藏
页码:341 / 349
页数:9
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